374 VIII. HEMATIN ENZYMES, I. CYTOCHROME SYSTEM 



that a series of hematin enzymes is required for the function of 

 cellular respiration. 



Equally great are the difficulties of quantitative estimation of 

 hematin respiration. The distribution of cytochrome oxidase and 

 cytochrome c in mammalian tissues has been studied carefully and 

 quantitative data are known. We are not yet certain, however, how 

 far results obtained by such studies are quantitatively representative 

 of the whole of the respiration catalyzed by the cytochrome system 

 in the intact cell. Inhibitors have been used to determine the part 

 of the total respiration catalyzed by the hematin enzymes. Such 

 data cover a wider range of organisms, but the interpretation of the 

 inhibition experiments is uncertain {cf. Section 5.4.). For all these 

 reasons an attempt at a comparative biochemistry of cellular respira- 

 tion would be premature. 



5.2. Pathways of Cellular Oxidation 

 through the Cytochrome System 



In Section 3. is summarized the evidence showing that atmospheric 

 oxygen reacts with a hematin enzyme (respiratory ferment, cyto- 

 chrome oxidase), which in turn oxidizes ferrous nonautoxidizable 

 hematin compounds (cytochromes) to their ferric form. The problem 

 of the autoxidation of the respiratory ferment will be discussed below 

 (Section 7.). It is not yet definitely proved which cytochrome is the 

 first to be oxidized by the oxidase. All oxidase preparations also 

 contain cytochrome a and the ferrous cytochrome a is probably the 

 one reacting directly with the ferric oxidase. This is also made likely 

 by the fact that the oxidation-reduction potential of cytochrome a 

 is slightly higher than that of cytochrome c {cf. below), although we 

 have discussed in Section 1. that this in itself cannot be accepted as 

 proof for the relative positions of cytochromes a and c in the reaction 

 chain (cf. Ball, 124). We have also seen that the cytochrome oxidase - 

 cytochrome a system does not react directly with the most important 

 substrate dehydrogenase systems. Cytochrome c and, in some 

 instances, cytochrome b are also required as intermediate electron 

 carriers, until finally one of these cytochromes reacts with a mono- 

 valent hydrogen donor. 



The way in which this reaction occurs has been formulated in Section 

 3.3.2. Of these monovalent hydrogen donors the flavoproteins are the most 

 important and best known. Cytochrome reductase, an alloxazine mono- 

 nucleotide protein, combines with cytochrome c to form a complex (K = 10"') 



